A Research Study to Compare Insulin 287 Once a Week to Insulin Glargine (100 Units/mL) Once a Day in People With Type 2 Diabetes.

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT03751657
Collaborator
(none)
247
49
2
13.6
5
0.4

Study Details

Study Description

Brief Summary

The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. The study participants will either get insulin 287 or insulin glargine (100 units/mL) - which treatment the participants get is decided by chance. The participants will need to inject their selves every day about the same time. Once a week the participant will need to take 1 extra injection on the same day of the week. The participants will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter using a finger prick, 2) write down different information in a paper diary daily and return this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2 weeks 5 times during the study.

Condition or Disease Intervention/Treatment Phase
  • Drug: Insulin icodec
  • Drug: Placebo (insulin 287)
  • Drug: Metformin
  • Drug: Dipeptidyl peptidase-4 inhibitors
  • Drug: Insulin glargine
  • Drug: Placebo (insulin glargine)
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
247 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Primary Purpose:
Treatment
Official Title:
An Investigational Trial Comparing the Efficacy and Safety of Once Weekly NNC0148-0287 C (Insulin 287) Versus Once Daily Insulin Glargine, Both in Combination With Metformin, With or Without DPP-4 Inhibitors, in Insulin naïve Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date :
Nov 29, 2018
Actual Primary Completion Date :
Dec 16, 2019
Actual Study Completion Date :
Jan 17, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Insulin 287

Participants will receive once weekly insulin 287 and once daily placebo in combination with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) during 26 weeks of treatment period.

Drug: Insulin icodec
Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL)
Other Names:
  • Insulin 287
  • Drug: Metformin
    Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.

    Drug: Dipeptidyl peptidase-4 inhibitors
    Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.

    Drug: Placebo (insulin glargine)
    Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.

    Active Comparator: Insulin glargine

    Participants will receive once daily insulin glargine and once weekly placebo in combination with metformin with or without DPP4i during 26 weeks of treatment period.

    Drug: Placebo (insulin 287)
    Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.

    Drug: Metformin
    Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.

    Drug: Dipeptidyl peptidase-4 inhibitors
    Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.

    Drug: Insulin glargine
    Insulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL).

    Outcome Measures

    Primary Outcome Measures

    1. Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)] [From baseline (Visit 2) to week 26 (Visit 28)]

      Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    2. Change in HbA1c [Millimoles/Mole (mmol/Mol)] [From baseline (Visit 2) to week 26 (Visit 28)]

      Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    Secondary Outcome Measures

    1. Change in Fasting Plasma Glucose [From baseline (Visit 2) to week 26 (Visit 28)]

      Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    2. 9-point Profile (Individual SMPG Values) [Week 26 (Visit 28)]

      Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    3. Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time [From baseline (Visit 2) to week 26 (Visit 28)]

      Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    4. Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time). [Week 26 (Visit 28)]

      Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    5. Fasting C-peptide [At week 26 (Visit 28)]

      Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    6. Change in Body Weight [From baseline (Visit 2) to week 26 (Visit 28)]

      Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    7. Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine [week 25 (Visit 27) and 26 (Visit 28)]

      Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.

    8. Number of Treatment Emergent Adverse Events (TEAEs) [From baseline (Visit 2) to week 31 (Visit 30)]

      An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.

    9. Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter) [From baseline (Visit 2) to week 26 (Visit 28)]

      Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and less than (<) 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.

    10. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3) [From baseline (Visit 2) to week 26 (Visit 28)]

      Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.

    11. Number of Severe Hypoglycaemic Episodes (Level 3) [From baseline (Visit 2) to week 26 (Visit 28)]

      Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.

    12. Change in Anti-insulin 287 Antibody Titres [From baseline (Visit 2) to week 31 (Visit 30)]

      Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.

    13. Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative) [From baseline (Visit 2) to week 31 (Visit 30)]

      Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.

    14. Change in Anti-insulin 287 Antibody Level [From baseline (Visit 2) to week 31 (Visit 30)]

      Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent

    • Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening

    • HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory

    • Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record) OR Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records)

    • Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes

    • Body mass index (BMI) less than or equal to 40.0 kg/m^2

    Exclusion Criteria:
    • Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation

    • Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation

    • Presently classified as being in New York Heart Association (NYHA) Class IV

    • Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes

    • Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids)

    • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novo Nordisk Investigational Site Lancaster California United States 93534
    2 Novo Nordisk Investigational Site Ventura California United States 93003
    3 Novo Nordisk Investigational Site Walnut Creek California United States 94598
    4 Novo Nordisk Investigational Site Roswell Georgia United States 30076
    5 Novo Nordisk Investigational Site Lexington Kentucky United States 40503
    6 Novo Nordisk Investigational Site Las Vegas Nevada United States 89128
    7 Novo Nordisk Investigational Site Charlotte North Carolina United States 28277
    8 Novo Nordisk Investigational Site Whiteville North Carolina United States 28472
    9 Novo Nordisk Investigational Site Chattanooga Tennessee United States 37404
    10 Novo Nordisk Investigational Site Chattanooga Tennessee United States 37411
    11 Novo Nordisk Investigational Site Austin Texas United States 78731
    12 Novo Nordisk Investigational Site Dallas Texas United States 75230
    13 Novo Nordisk Investigational Site Dallas Texas United States 75390-9302
    14 Novo Nordisk Investigational Site Renton Washington United States 98057
    15 Novo Nordisk Investigational Site Halifax Nova Scotia Canada B3H 1V7
    16 Novo Nordisk Investigational Site Brampton Ontario Canada L6S 0C6
    17 Novo Nordisk Investigational Site Concord Ontario Canada L4K 4M2
    18 Novo Nordisk Investigational Site Etobicoke Ontario Canada M9R 4E1
    19 Novo Nordisk Investigational Site Hamilton Ontario Canada L8M 1K7
    20 Novo Nordisk Investigational Site Sarnia Ontario Canada N7T 4X3
    21 Novo Nordisk Investigational Site St-Marc-des-Carrières Quebec Canada G0A 4B0
    22 Novo Nordisk Investigational Site Brno Czechia 62500
    23 Novo Nordisk Investigational Site Pardubice Czechia 530 02
    24 Novo Nordisk Investigational Site Praha 1 Czechia 110 00
    25 Novo Nordisk Investigational Site Praha 4 Czechia 149 00
    26 Novo Nordisk Investigational Site Praha 5 Czechia 150 00
    27 Novo Nordisk Investigational Site Praha 8 Czechia 181 00
    28 Novo Nordisk Investigational Site Praha Czechia 128 08
    29 Novo Nordisk Investigational Site Rakovník Czechia 269 01
    30 Novo Nordisk Investigational Site Slaný Czechia 27401
    31 Novo Nordisk Investigational Site Athens Greece 115 25
    32 Novo Nordisk Investigational Site Athens Greece GR-11527
    33 Novo Nordisk Investigational Site Thessaloniki Greece GR-54636
    34 Novo Nordisk Investigational Site Thessaloniki Greece GR-54642
    35 Novo Nordisk Investigational Site Thessaloniki Greece GR-57010
    36 Novo Nordisk Investigational Site Bialystok Poland 15-404
    37 Novo Nordisk Investigational Site Gdansk Poland 80-546
    38 Novo Nordisk Investigational Site Lodz Poland 90-132
    39 Novo Nordisk Investigational Site Poznan Poland 61-251
    40 Novo Nordisk Investigational Site Warsaw Poland 00-465
    41 Novo Nordisk Investigational Site Wierzchoslawice Poland 33-122
    42 Novo Nordisk Investigational Site Bratislava Slovakia 821 02
    43 Novo Nordisk Investigational Site Bratislava Slovakia 851 01
    44 Novo Nordisk Investigational Site Kosice Slovakia 040 01
    45 Novo Nordisk Investigational Site Moldava nad Bodvou Slovakia 045 01
    46 Novo Nordisk Investigational Site Sahy Slovakia 93601
    47 Novo Nordisk Investigational Site Trencin Slovakia 91101
    48 Novo Nordisk Investigational Site Koper Slovenia SI-6000
    49 Novo Nordisk Investigational Site Ljubljana Slovenia SI-1000

    Sponsors and Collaborators

    • Novo Nordisk A/S

    Investigators

    • Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT03751657
    Other Study ID Numbers:
    • NN1436-4383
    • U1111-1208-4124
    • 2018-000322-63
    First Posted:
    Nov 23, 2018
    Last Update Posted:
    Apr 2, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details The trial was conducted at 49 sites in Canada (7), Czech Republic (9), Greece (5), Poland (6), Slovakia (6),Slovenia (2) and United States (14). One site in the United States screened, but didn't randomise any participant.
    Pre-assignment Detail Insulin-naïve participants with Type 2 Diabetes (T2D) inadequately controlled on metformin with or without dipeptidyl peptidase 4 inhibitor (DPP4i) were randomized in a 1:1 manner to receive once weekly insulin 287 and once daily placebo or once weekly placebo and once daily insulin glargine subcutaneously (s.c).
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Period Title: Overall Study
    STARTED 125 122
    COMPLETED 122 119
    NOT COMPLETED 3 3

    Baseline Characteristics

    Arm/Group Title Insulin 287 Insulin Glargine Total
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Total of all reporting groups
    Overall Participants 125 122 247
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    59.7
    (8.2)
    59.4
    (9.5)
    59.6
    (8.9)
    Sex: Female, Male (Count of Participants)
    Female
    55
    44%
    53
    43.4%
    108
    43.7%
    Male
    70
    56%
    69
    56.6%
    139
    56.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    10
    8%
    6
    4.9%
    16
    6.5%
    Not Hispanic or Latino
    115
    92%
    116
    95.1%
    231
    93.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    8
    6.4%
    4
    3.3%
    12
    4.9%
    Native Hawaiian or Other Pacific Islander
    1
    0.8%
    0
    0%
    1
    0.4%
    Black or African American
    7
    5.6%
    5
    4.1%
    12
    4.9%
    White
    109
    87.2%
    113
    92.6%
    222
    89.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
    Description Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 122 120
    Least Squares Mean (Standard Error) [Percentage point of HbA1c]
    -1.33
    (0.07)
    -1.15
    (0.07)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin 287, Insulin Glargine
    Comments The response and change from baseline in response after 26 weeks are analysed using a linear mixed model for repeated measures (MMRM) with an unstructured covariance matrix and treatment, region, use of DPP-4 inhibitor and visit as fixed factors, and baseline response as covariate. Furthermore, the model includes the interaction between visit and all explanatory variables.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0818
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Treatment difference
    Estimated Value -0.18
    Confidence Interval (2-Sided) 95%
    -0.38 to 0.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Change in Fasting Plasma Glucose
    Description Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 121 116
    Least Squares Mean (Standard Error) [mmol/l]
    -3.20
    (0.16)
    -2.99
    (0.16)
    3. Secondary Outcome
    Title 9-point Profile (Individual SMPG Values)
    Description Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame Week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 125 122
    Before breakfast
    5.70
    (0.19)
    6.19
    (0.19)
    90 minutes after start of breakfast
    7.90
    (0.19)
    8.51
    (0.19)
    Before lunch
    6.09
    (0.19)
    6.19
    (0.19)
    90 minutes after start of lunch
    7.83
    (0.19)
    8.50
    (0.19)
    Before main evening meal
    6.55
    (0.19)
    6.96
    (0.19)
    90 minutes after the start of main evening meal
    8.01
    (0.19)
    8.47
    (0.19)
    Before bedtime
    7.35
    (0.19)
    7.87
    (0.19)
    At 4:00 a.m.
    5.72
    (0.19)
    5.98
    (0.19)
    Before breakfast the following day
    5.74
    (0.19)
    6.05
    (0.19)
    4. Secondary Outcome
    Title Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
    Description Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 112 111
    Least Squares Mean (Standard Error) [mmol/l]
    -2.70
    (0.12)
    -2.26
    (0.12)
    5. Secondary Outcome
    Title Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
    Description Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame Week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 112 111
    Least Squares Mean (95% Confidence Interval) [mmol/l]
    0.92
    0.94
    6. Secondary Outcome
    Title Fasting C-peptide
    Description Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame At week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 115 112
    Least Squares Mean (95% Confidence Interval) [Nanomoles per liter (nmol/l)]
    0.44
    0.47
    7. Secondary Outcome
    Title Change in Body Weight
    Description Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 122 119
    Least Squares Mean (Standard Error) [Kilogram]
    1.49
    (0.36)
    1.56
    (0.37)
    8. Secondary Outcome
    Title Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
    Description Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame week 25 (Visit 27) and 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 120 117
    Least Squares Mean (95% Confidence Interval) [Units of Insulin]
    229.06
    284.05
    9. Secondary Outcome
    Title Number of Treatment Emergent Adverse Events (TEAEs)
    Description An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.
    Time Frame From baseline (Visit 2) to week 31 (Visit 30)

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set (SAS) included all participants who received at least one dose of the investigational product or comparator.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 125 122
    Number [Events]
    229
    158
    10. Secondary Outcome
    Title Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
    Description Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and less than (<) 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    SAS included all participants who received at least one dose of the investigational product or comparator.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 125 122
    Number [Episodes]
    358
    145
    11. Secondary Outcome
    Title Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
    Description Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    SAS included all participants who received at least one dose of the investigational product or comparator.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 125 122
    Number [Episodes]
    38
    31
    12. Secondary Outcome
    Title Number of Severe Hypoglycaemic Episodes (Level 3)
    Description Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    SAS included all participants who received at least one dose of the investigational product or comparator.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 125 122
    Number [Episodes]
    1
    0
    13. Secondary Outcome
    Title Change in Anti-insulin 287 Antibody Titres
    Description Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
    Time Frame From baseline (Visit 2) to week 31 (Visit 30)

    Outcome Measure Data

    Analysis Population Description
    SAS included all participants who received at least one dose of the investigational product or comparator. Overall number of participants analysed = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 119
    Mean (Standard Deviation) [Antibody titers]
    979.9
    (3177.9)
    14. Secondary Outcome
    Title Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
    Description Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
    Time Frame From baseline (Visit 2) to week 31 (Visit 30)

    Outcome Measure Data

    Analysis Population Description
    SAS included all participants who received at least one dose of the investigational product or comparator.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 125 122
    Negative
    0
    0%
    1
    0.8%
    Positive
    0
    0%
    0
    0%
    Unknown
    1
    0.8%
    9
    7.4%
    Not Applicable
    124
    99.2%
    112
    91.8%
    Negative
    9
    7.2%
    0
    0%
    Positive
    86
    68.8%
    26
    21.3%
    Unknown
    0
    0%
    0
    0%
    Not Applicable
    25
    20%
    89
    73%
    15. Primary Outcome
    Title Change in HbA1c [Millimoles/Mole (mmol/Mol)]
    Description Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
    Time Frame From baseline (Visit 2) to week 26 (Visit 28)

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomised participants. "Number of Participants Analyzed" = Number of participants contributing to the analysis.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 122 120
    Least Squares Mean (Standard Error) [mmol/mol]
    -14.51
    (0.79)
    -12.54
    (0.80)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Insulin 287, Insulin Glargine
    Comments The response and change from baseline in response after 26 weeks are analysed using a linear MMRM with an unstructured covariance matrix and treatment, region, use of DPP-4 inhibitor and visit as fixed factors, and baseline response as covariate.Furthermore, the model includes the interaction between visit and all explanatory variables.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0818
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Treatment difference
    Estimated Value -1.97
    Confidence Interval (2-Sided) 95%
    -4.19 to 0.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    16. Secondary Outcome
    Title Change in Anti-insulin 287 Antibody Level
    Description Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.
    Time Frame From baseline (Visit 2) to week 31 (Visit 30)

    Outcome Measure Data

    Analysis Population Description
    Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    Measure Participants 0 0

    Adverse Events

    Time Frame Week 0 to Week 31 Results are based on the SAS which included all participants who received at least one dose of Insulin 287 or Insulin glargine. The SAS included all participants who received at least one dose of the investigational product or comparator.
    Adverse Event Reporting Description A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.
    Arm/Group Title Insulin 287 Insulin Glargine
    Arm/Group Description Participants were to receive once weekly s.c. injection of insulin 287 using PDS290 prefilled pen-injector at a starting dose of 70 units (U) and once daily placebo for 26 weeks. The insulin dose was then adjusted once weekly to reach the glycaemic target of 3.9-6.0 millimoles per liter (mmol/L) based on 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 28 U, and 3.0-3.8- dose reduced by 14 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 14U, and >7.0 mmol/L- dose increased by 28U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns. Participants were to receive once daily s.c injection of Insulin glargine using 10 ml vial and syringe at a starting dose of 10 U and once weekly placebo for 26 weeks. The insulin dose was then adjusted to reach the glycaemic target of 3.9-6.0 mmol/L based on 3 pre-breakfast SMPG values measured on 2 previous days and on the day of the titration. If at least one pre-breakfast SMPG value was: < 3.0 mmol/L- dose reduced by 4 U, and 3.0-3.8 dose reduced by 2 U. Otherwise, the dose adjustment was based on the mean of SMPG values. If the mean was: 3.9-6.0 mmol/L- no adjustment; 6.1-7.0 mmol/L- dose increased by 2 U, and >7.0 mmol/L- dose increased by 4 U. All participants used metformin with or without DPP4i at the stable, pre-trial dose and at the same frequency unless due to safety concerns.
    All Cause Mortality
    Insulin 287 Insulin Glargine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/125 (0%) 0/122 (0%)
    Serious Adverse Events
    Insulin 287 Insulin Glargine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/125 (1.6%) 3/122 (2.5%)
    Blood and lymphatic system disorders
    Anaemia 0/125 (0%) 0 1/122 (0.8%) 1
    Leukocytosis 0/125 (0%) 0 1/122 (0.8%) 1
    Cardiac disorders
    Coronary artery disease 0/125 (0%) 0 1/122 (0.8%) 1
    Tachycardia 0/125 (0%) 0 1/122 (0.8%) 1
    Gastrointestinal disorders
    Melaena 0/125 (0%) 0 1/122 (0.8%) 1
    Hepatobiliary disorders
    Hepatosplenomegaly 0/125 (0%) 0 1/122 (0.8%) 1
    Infections and infestations
    Emphysematous pyelonephritis 0/125 (0%) 0 1/122 (0.8%) 1
    Injury, poisoning and procedural complications
    Lower limb fracture 1/125 (0.8%) 1 0/122 (0%) 0
    Metabolism and nutrition disorders
    Hypomagnesaemia 0/125 (0%) 0 1/122 (0.8%) 1
    Nervous system disorders
    Cerebral disorder 0/125 (0%) 0 1/122 (0.8%) 1
    Renal and urinary disorders
    Acute kidney injury 0/125 (0%) 0 1/122 (0.8%) 1
    Azotaemia 0/125 (0%) 0 1/122 (0.8%) 1
    Hydronephrosis 0/125 (0%) 0 1/122 (0.8%) 1
    Reproductive system and breast disorders
    Metrorrhagia 1/125 (0.8%) 1 0/122 (0%) 0
    Other (Not Including Serious) Adverse Events
    Insulin 287 Insulin Glargine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 26/125 (20.8%) 16/122 (13.1%)
    Infections and infestations
    Nasopharyngitis 10/125 (8%) 12 8/122 (6.6%) 9
    Upper respiratory tract infection 7/125 (5.6%) 7 6/122 (4.9%) 8
    Nervous system disorders
    Headache 14/125 (11.2%) 31 3/122 (2.5%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.

    Results Point of Contact

    Name/Title Clinical Reporting Anchor and Disclosure (1452)
    Organization Novo Nordisk A/S
    Phone (+1)866-867-7178
    Email clinicaltrials@novonordisk.com
    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT03751657
    Other Study ID Numbers:
    • NN1436-4383
    • U1111-1208-4124
    • 2018-000322-63
    First Posted:
    Nov 23, 2018
    Last Update Posted:
    Apr 2, 2021
    Last Verified:
    Mar 1, 2021